Download Exercise training increases arterial compliance in patients with

Clinical Science (2002) 102, 1–7 (Printed in Great Britain)
Exercise training increases arterial compliance
in patients with congestive heart failure
Melinda M. PARNELL, Diane P. HOLST and David M. KAYE
Alfred Heart Centre and Alfred Baker Medical Unit, Baker Medical Research Institute, P.O. Box 6492, St Kilda Road Central,
Melbourne, Victoria 8008, Australia
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Systemic arterial compliance (SAC) makes an important contribution to cardiac afterload, and
thus is a significant determinant of left ventricular work. Previous studies have suggested that
arterial compliance may be reduced in patients with congestive heart failure (CHF), and that SAC
is increased after a 4-week exercise training programme in healthy, sedentary individuals. The
present study aimed to investigate the effects of an 8-week exercise training programme on
arterial mechanical properties, left ventricular performance and quality of life in CHF patients.
A total of 21 patients with NYHA class II or III CHF (meanpS.D. age 55p13 years) were
randomly allocated to either an 8-week exercise training group or a ‘ usual lifestyle ’ control
group. SAC, as determined non-invasively using applanation tonometry and Doppler aortic
velocimetry, increased from 0.57p0.11 to 0.77p0.14 arbitrary compliance units (meanpS.E.M. ;
P l 0.01) in the exercise group, while no change occurred in the control group. Left ventricular
structure and function was assessed by echocardiography, and these parameters were unchanged
over the 8-week study period. Exercise training significantly increased exercise capacity,
measured by a 6-min walking test (474p27 to 547p34 m ; P l 0.008). Quality of life, as assessed
using the Minnesota Living with Heart Failure Evaluation, demonstrated a decrease in heart
failure symptoms from 46p7 to 24p5 units (P l 0.01) following the exercise training
programme. These data show that exercise training improves SAC in patients with CHF. The
accompanying improvement in exercise capacity may be due, in part, to an improvement in
arterial function.
INTRODUCTION
Congestive heart failure (CHF) is characterized by
reduced ventricular performance in conjunction with
neurohormonal activation and fluid retention. As a
component of this syndrome, elevated peripheral vascular
resistance is classically observed, representing the consequence of the vasoconstrictor action of neurohormones
on resistance vessels. In this context, the clinical utility of
vasodilator drugs that reduce peripheral vascular resistance, and thereby cardiac afterload, is well recognized.
Recently it has become increasingly appreciated that the
mechanical properties of the large arteries also contribute
significantly to afterload. Systemic arterial compliance
(SAC) has been shown to decrease with age [1] and in
some cardiovascular disorders, such as hypertension
[1,2]. It is thought that arterial compliance is reduced in
CHF patients [3,4], although the implications of this
observation remain uncertain.
In addition to pharmacological therapy, participation
in a moderate exercise programme has been shown to
reduce fatigue and dyspnoea [5,6], symptoms commonly
Key words: arteries, exercise, heart failure, mechanical properties.
Abbreviations : a.c.u., arbitrary compliance units ; CHF, congestive heart failure ; E\A ratio, E-wave velocity\A-wave velocity ;
PWV, pulse wave velocity ; SAC, systemic arterial compliance.
Correspondence: Dr David Kaye (e-mail david.kaye!baker.edu.au).
# 2002 The Biochemical Society and the Medical Research Society
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M. M. Parnell, D. P. Holst and D. M. Kaye
associated with the daily lifestyle of patients with heart
failure. However, the mechanism(s) by which exercise
improves these parameters is uncertain. In healthy
subjects, it is now well established that aerobic training
improves arterial compliance [7–11]. To date, the effect of
an exercise training programme on arterial compliance in
CHF has not been investigated.
Reduced SAC is potentially disadvantageous in
patients with CHF, due to an adverse impact on
ventricular performance ; effects include increased cardiac
afterload and arterial impedance, as well as reduced
diastolic pressure and thus coronary blood flow. It has
been shown that regional arterial compliance is decreased
in heart failure patients [3,4,12,13] ; however, SAC has
not been determined in CHF patients to date. It also
remains unclear whether heart failure patients can exercise sufficiently to improve arterial compliance. In
order to address these issues, the aim of the present study
was to investigate the effects of an 8-week exercise
training programme on SAC and quality of life in CHF
patients.
METHODS
Subjects
A total of 21 patients (meanpS.D. age 55p13 years) with
stable CHF (meanpS.E.M. left ventricular ejection
fraction 25p2 %) were recruited from the Heart Failure
Clinic at the Alfred Hospital. NYHA class II and III
patients on stable anti-failure therapy aged between 17
and 70 years, who were able to participate in an exercise
programme, were selected for the study. Prior to experimentation, subjects gave written informed consent ;
in addition, the research was carried out in accordance
with the Declaration of Helsinki (1989) of the World
Medical Association, and the study was approved by The
Alfred Healthcare Group Ethics Committee.
Protocol
Patients recruited from the Alfred Heart Failure Clinic
were allocated randomly either to an 8-week exercise
programme or to continue with their usual lifestyle. The
patients allocated to the ‘ usual living ’ group were
instructed not to change their regular daily activities for
the 8-week study duration. The exercise programme
was conducted over 8 weeks ; patients were required
to exercise at 50–60 % of maximum heart rate, and to
progressively increase their exercise duration from three
30 min sessions per week to approx. 60 min per day on
5–7 days per week. An individualized programme of
walking, light hand weights and stationary cycling was
tailored according to an individual’s capacities, and
was increased progressively over the 8-week period according to individual responses. Measurements of arterial
# 2002 The Biochemical Society and the Medical Research Society
compliance, pulse wave velocity (PWV), blood pressure,
quality of life, left ventricular function and exercise
capacity were performed at baseline and after the 8-week
intervention.
Assessment of arterial mechanics
SAC, broadly defined as the change in volume of a vessel
associated with a given change in pressure within that
vessel [8], was determined by the area method described
by Liu et al. [14] and validated in our laboratory [7]. The
technique involves the simultaneous non-invasive measurement of ascending aortic blood flow velocity and right
carotid arterial pressure, as described previously [7,15].
Ascending aortic blood flow velocity was measured by
continuous-wave Doppler flow velocimetry with a
3.5 MHz transducer (Multi-doplex ; Huntleigh Technology, Cardiff, U.K.) placed at the suprasternal notch.
The product of aortic flow velocity and left ventricular
outflow tract area was used to calculate aortic volumetric
flow. An estimate of central systolic pressure was derived
from applanation of the proximal right carotid artery
using a pressure transducer (Miller Mikro-Tip SPT-301 ;
Miller Instruments, Houston, TX, U.S.A.). Pressures
were calibrated by simultaneous measurement of brachial
arterial pressure, using a Dinamap vital signs monitor
(18465X ; Dinamap, Critikon, FL, U.S.A.). Arterial compliance was reported in arbitrary compliance units
(a.c.u.), dimensionally equal to ml\mmHg. [7] PWV,
which is inversely related to arterial compliance, was
measured centrally (between the right carotid artery and
the right femoral artery) and peripherally (between the
right femoral artery and the right dorsalis pedis artery) by
simultaneous applanation tonometry [15].
Augmentation index
Carotid pressure waveforms obtained for the determination of SAC were used to calculate the augmentation
index, defined as the difference between the first and
second systolic peaks of the central arterial waveform,
expressed as a percentage of pulse pressure [16]. Pressure
data for each cardiac cycle selected were linearly detrended assuming equality of pressure at the start and end
of each cardiac cycle, and then scaled to brachial artery
mean and diastolic pressure. The features of the carotid
arterial waveform were characterized, including pressure
at inflection, peak systolic pressure and augmented
pressure [16]. The values of augmentation index and
augmented pressure were defined as positive or negative
depending on whether pressure at inflection occurred
before or after peak systolic pressure.
Assessment of cardiac function
A trained operator who was blinded to the training status
of each subject performed and interpreted all measure-
Exercise training in congestive heart failure
ments with the use of two-dimensional echocardiography
(Hewlett–Packard 77020A). M-mode images of the left
ventricle using the parasternal short axis view at the level
of the mitral chordae were used to obtain left ventricular
dimensions. Flow through the mitral valve was measured
via pulsed-wave Doppler echocardiography.
Assessment of quality of life and functional
performance
Quality of life was assessed by the completion by the
patient of a questionnaire, the Minnesota Living with
Heart Failure Evaluation [17]. Functional performance
was determined by a 6-min walking test, as described
previously [18]. Distance walked, heart rate and perceived
exertion were the primary measurements taken during
the walking test.
Statistical analysis
Statistical analysis was performed using SPSS Version
10.0 (SPSS Inc., Chicago, IL, U.S.A.). The significance
level employed was P 0.05. Repeated-measures
ANOVA was performed for blood pressure, weight,
SAC, PWV, left ventricular dimensions, mitral flow,
quality of life and the exercise test. All results, including
those in Figures, are presented as meanspS.E.M., excluding age, which is given as meanpS.D.
RESULTS
A total of 21 patients with moderate to severe CHF were
included in the study, of which 11 participated in the
exercise programme and 10 acted as control subjects. The
two groups were similar in age (controls, 53p11 years ;
exercise group, 57p15 years ; Table 1) and body mass
Table 1
Baseline characteristics of the study groups
LVEF, left ventricular ejection function.
Characteristic
Exercise group
Control group
NHYA class (II/III)
Gender (male/female)
Age (years)
LVEF ( %)
Diagnosis (ischaemic/non-ischaemic)
7/4
10/1
57p15
25p2
2/9
7/3
9/1
53p11
24p3
4/6
Table 2
Figure 1 Exercise capacity in the two groups of CHF
patients, as assessed by distance walked during a 6-min
walking test
The control group is represented by closed bars, and the exercise group by open
bars. Significance of differences : *P l 0.008.
index (controls, 26.0p0.7 kg:m−# ; exercise group,
27.4p1.7 kg:m−#), and there were no significant differences in resting heart rate or blood pressure between
the groups at baseline (see Table 3). All patients were
taking the typical range of anti-failure medications
(Table 2) ; these regimes had been stable for at least
2 weeks before beginning the study, and remained stable
throughout the study. There were significantly more
(P l 0.03) patients taking digoxin in the control group
than in exercise group. All patients were previous or
non-smokers.
Effects of exercise training in CHF
Following the 8-week exercise training programme,
patients walked significantly further during the 6-min
walking test (before, 474p27 m ; after, 547p34 m ; P l
0.008), while the control group showed no change in
exercise capacity (before, 517p21 m ; after, 515p29 m)
(Figure 1). Moreover, there was a decrease in heart rate
following participation in the exercise programme (from
66p3 to 62p2 beats\min ; P l 0.037), whereas there was
no significant change in ‘ usual living ’ group (from 76p5
to 70p2 beats\min). There was no significant difference
Drug regimes of the subjects
ACEi, angiotensin-converting enzyme inhibitors. Significance of difference : *P l 0.03 compared with exercise group.
Subjects taking drug ( %)
Subjects
ACEi
Diuretics
Aspirin
Digoxin
β-Blockers
Warfarin
Total
Exercise group
Control group
100
100
100
100
100
100
57
45
70
67
45
90*
76
72
80
52
36
70
# 2002 The Biochemical Society and the Medical Research Society
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M. M. Parnell, D. P. Holst and D. M. Kaye
Table 3
Cardiovascular parameters
PP, pulse pressure ; SBP, systolic blood pressure ; DBP, diastolic blood pressure ; MAP, mean arterial pressure ; AI, augmentation
index ; LVIDd, end-diastolic left ventricular internal diameter ; LVIDs, end-systolic left ventricular internal diameter ;
IVST, interventricular septum thickness ; PWT, posterior wall thickness ; FS, fractional shortening ; EWV, E-wave velocity ;
AWV, A-wave velocity.
Exercise group
Control group
Parameter
Baseline
8 weeks
Baseline
8 weeks
Heart rate (beats/min)
Central PP (mmHg)
SBP (mmHg)
DBP (mmHg)
MAP (mmHg)
AI ( %)
LVIDd (cm)
LVIDs (cm)
IVST (cm)
PWT (cm)
FS ( %)
EWV (cm:s−1)
Deceleration time (ms)
AWV (cm:s−1)
E/A
66p3
46p6
106p7
62p2
79p5
5.73p3.33
6.79p0.36
5.66p0.42
1.04p0.09
1.00p0.05
17.61p2.22
81.7p8.7
219.4p21.8
52.8p7.6
1.96p0.38
62p2
48p5
108p8
60p3
79p6
7.27p2.63
6.89p0.24
5.67p0.3
1.07p0.12
0.98p0.07
18.10p2.07
83.5p5.6
225.8p18.6
56.3p7.4
1.77p0.36
75p7
42p5
110p6
67p2
83p3
2.10p2.63
6.93p0.41
5.83p0.36
0.91p0.07
0.96p0.06
15.74p1.35
77.5p7.7
189.4p21.7
58.1p10.9
1.74p0.42
76p6
38p4
104p5
66p2
81p4
3.20p1.47
6.92p0.35
5.89p0.37
0.92p0.11
1.10p0.16
15.14p2.31
74.8p9.8
185.7p17.5
53.2p10.8
1.62p0.38
Failure Evaluation, decreased from 46p7 to 24p5 units
(P l 0.01) in the exercise training group (Figure 2).
Arterial mechanics
Figure 2
Quality of life in the two groups of CHF patients
Quality of life was assessed using the Minnesota Living with Heart Failure
Evaluation, both at baseline and after the 8-week study period, in the control
(closed bars) and exercise (open bars) groups. Significance of differences :
†P l 0.01.
in resting heart rate between the two groups at baseline ;
however, after 8 weeks, the exercise group had a
significantly lower heart rate when compared with the
control group (P l 0.03). There were no changes in
resting blood pressure in either the exercise or the control
group following the 8-week study period (Table 3).
Quality of life did not differ between the two groups at
baseline. However, following involvement in the exercise
programme, the symptoms associated with heart failure,
determined using the Minnesota Living with Heart
# 2002 The Biochemical Society and the Medical Research Society
There were no differences in arterial mechanics between
the exercise and control groups at baseline (Figure 3).
While the control group showed no change in SAC after
8 weeks of usual living [before, 0.59p0.10 a.c.u. (95 %
confidence intervals 0.34–0.83 a.c.u.) ; after, 0.55p
0.08 a.c.u. (0.30–0.81 a.c.u.)], the exercise training group
demonstrated a significant increase in SAC following the
training programme [before, 0.57p0.11 a.c.u. (0.34–
0.80 a.c.u.) ; after, 0.77p0.14 a.c.u. (0.53–1.02 a.c.u.) ;
P l 0.01] (Figure 3, upper panel). However, neither
central nor peripheral PWV had changed in either the
exercise group or the control group after the 8-week
study period (Figure 3, lower panel). These improvements in SAC are not explained by changes in mean
arterial pressure, pulse pressure or wave reflection
(augmentation index), the values of which remained
similar throughout the study (Table 3).
Cardiac function
At baseline, there was no difference in left ventricular
ejection fraction between the control and exercise groups
(Table 1). Furthermore, left ventricular dimensions and
function were unchanged following the 8-week intervention period in both the control and exercise groups
(Table 3).
Exercise training in congestive heart failure
study were to determine the effects of an exercise training
programme on arterial compliance in CHF patients. The
effects of this exercise programme on left ventricular
structure and function and on the patients ’ quality of life
were also investigated.
Exercise capacity and quality of life
Figure 3 Measures of arterial mechanics in the two groups
of patients
Upper panel : SAC at baseline and after the 8-week study period in the control
(closed bars) and exercise (open bars) groups. Significance of differences :
‡P l 0.01. Lower panel : central and peripheral PWV in the control (left
panels) and exercise (right panels) groups before (closed bars) and after (open
bars) the 8-week study period.
DISCUSSION
CHF is a common cardiovascular disorder characterized
by poor cardiac performance, fluid retention and vasoconstriction. Vasodilator drug therapy alleviates heart
failure symptoms by reducing peripheral vascular resistance and thereby afterload. Recently it has also
become apparent that the mechanical properties of large
arteries (arterial compliance) may also contribute significantly to afterload. It is recognized that the symptomatic improvements in CHF patients following an
exercise programme are due, in part, to an attenuation of
the peripheral vascular abnormalities, rather than to
central haemodynamic changes [19] ; however, the mechanisms responsible for the exercise-induced improvements in heart failure symptoms have not been entirely
identified. Previous studies have shown that SAC increases following an exercise training programme in
healthy subjects [7] ; therefore the aims of the present
CHF patients were able to walk significantly further
during the 6-min walking test following the 8-week
training programme, whereas for the control group the
distance walked remained unchanged. To our knowledge,
the present study is the first report in which the effects of
this type of training regime (a combination of light
weights and aerobic exercise using both cycling and
walking) has been examined in heart failure patients. It is
well documented that aerobic training alone results in an
improvement in exercise capacity in CHF patients
[5,6,20,21], and a recent study demonstrated an improvement in muscular strength and peak oxygen consumption in CHF patients enrolled in an 8-week circuit
weight training programme [22] ; however, results from
combined training programmes have not been documented. Not only did the training programme in the
present study produce an improvement in the exercise
capacity of CHF patients, an improvement was also
evident in their quality of life, which supports previous
studies on exercise training in CHF [6,20]. By improving
fitness and strength with involvement in the present
exercise programme, quality of life may have improved
due to a combination of increases in patient confidence
and in physical capacity.
Arterial mechanics
In the present study we demonstrated that an exercise
training programme caused an increase in SAC in patients
with CHF, independent of any change in mean arterial
blood pressure and central pulse pressure. Reduced
arterial compliance has been shown to increase left
ventricular end-systolic stress [12] and afterload [8], and
to decrease coronary perfusion [23]. As a corollary, an
improvement in SAC would reduce the afterload placed
on the left ventricle, decreasing left ventricular endsystolic stress and increasing coronary perfusion. Kelly et
al. [24] demonstrated that an acute decrease in arterial
compliance was accompanied by a 32 % increase in
myocardial oxygen demand. Therefore the 35 % increase
in arterial compliance demonstrated in the present study
may have resulted in a significant decrease in myocardial
oxygen demand.
Although improvements were evident in SAC following exercise training, no improvements were evident
in PWV or the augmentation index. Central PWV did
show a slight, but non-significant, improvement following exercise training (from 8.32p0.86 to 8.62p
0.94 m:s−"), raising the possibility that a longer exercise
programme or greater patient numbers may produce a
# 2002 The Biochemical Society and the Medical Research Society
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M. M. Parnell, D. P. Holst and D. M. Kaye
significant change. The augmentation index, derived from
carotid tonometry, also demonstrated no change following exercise, indicating no change in pulse wave
reflection. This supports the PWV data, further suggesting that a longer exercise programme will be necessary to establish an improvement. As SAC is determined
using flow through the ascending aorta as a determinant
of whole-body arterial compliance, it is perhaps concentrating on the changes in the ascending aorta, a section
eliminated from the PWV calculations [10], and this may
account for the discrepancy between the two results.
It is well understood that endothelium-dependent
vasodilation is impaired in CHF [25–28]. Hambrecht and
colleagues [28] showed that an improvement in endothelial function in heart failure patients may be
associated with an increase in exercise capacity. Further,
it has been suggested that regular physical exercise
improves endothelial nitric oxide formation and consequent vasodilation of the skeletal muscle vasculature. In
the context of the present study, it has been suggested
that repetitive increases in flow caused by physical
training result in an up-regulation of nitric oxide production, thereby reducing peripheral vascular tone [25].
As endothelial dysfunction has been proposed to reduce
arterial distensibility [27], an improvement in the function of the endothelium following exercise training may
have contributed to the increased arterial compliance
demonstrated in the present study.
It is also well understood that sympathetic activity is
increased in CHF [29,30]. Grassi et al. [31] suggested that
the reduction in radial arterial compliance observed in
their study could have been a consequence of sympathetic
activation. There is mounting evidence that the beneficial
effect of endurance exercise training in heart failure
patients occurs via neurohumoral modulation, particularly through a reduction in sympathetic activity [32]. A
study of an exercise training programme involving 20 min
sessions on 5 days per week for 8 weeks showed a shift
from sympathetic activity towards enhanced vagal activity after training [6]. As exercise capacity increased in
the present study, sympathetic activation may have
decreased, lowering vasoconstrictor concentrations, thus
allowing greater relaxation of the vessels and consequently increasing arterial compliance.
As an alternative to functional changes as an explanation for the effects of exercise training on arterial
compliance, intrinsic alterations in the vessel wall have
also been proposed. Kingwell et al. [9] demonstrated that
an elevation in arterial compliance following spontaneous
running in Wistar–Kyoto rats may have a structural basis,
whereby the loading of collagen and elastin may be
altered, and not be the result of reduced blood pressure or
vasodilation. Other possible causes of the improvement
in arterial compliance could be decreased wall thickness
or intrinsic changes in wall composition and\or smooth
muscle activation.
# 2002 The Biochemical Society and the Medical Research Society
Cardiac structure and function
No changes were demonstrated in left ventricular structure in the present study. Previous work has largely
shown that training has no direct influence, either
beneficial or detrimental, on the myocardium in CHF
[33]. However, in healthy subjects, increases in left
ventricular diameters are apparent after 4 weeks of
exercise training [34]. It is thought that the reduced stress
and afterload induced following an exercise programme
may induce structural changes, but a longer follow-up
period may be required to illustrate these changes in
CHF patients. Although the E\A ratio (E-wave
velocity\A-wave velocity) has been demonstrated to
improve following an exercise programme in healthy
subjects [34], the present study showed no variation in
either E\A ratio or deceleration time, demonstrating no
change in diastolic dysfunction. The lack of a change in
ventricular function parameters suggests that training has
no direct effect upon the heart, and that the observed
beneficial effect may occur in the peripheral vascular
system. It has been suggested that the exercise-induced
increase in sympathetic activation could contribute to an
acute decrease in diastolic function in CHF patients,
which may persist for at least 24 h following an exercise
bout [35]. This information raises the question of
exercise frequency in CHF patients, as adequate periods
between exercise episodes may be essential to reduce the
risk of the progression of heart failure during long-term
training.
Conclusion
This study demonstrates for the first time that a tailored
exercise programme increases SAC in CHF patients. A
restoration of endothelial function through an exercise
training programme may play a major role in the
improvement in SAC. While there were no changes in
either the structure or the function of the left ventricle
following the exercise training programme, indices of
improvement in the patients’ quality of life was evident.
The maintenance and improvement of arterial compliance, as occurred in the present study in response to an
exercise training programme, may be of great benefit to
CHF patients, by reducing left ventricular afterload and
improving coronary perfusion.
ACKNOWLEDGMENTS
We thank Elizabeth Dewar and Karen Murchie for their
technical assistance. Thanks are due also to Jennifer
Patrick and Lynn Carter at Caulfield Cardiac Rehabilitation Unit. The helpful advice of Dr Jim Cameron and
Dr Bronwyn Kingwell is gratefully acknowledged. An
Institute Grant to the Baker Medical Research Institute
from the National Health and Medical Research Council
of Australia supported this study. M. M. P. is the
Exercise training in congestive heart failure
recipient of a Baker Medical Research Institute Biomedical Research Scholarship.
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Received 29 March 2001/2 July 2001; accepted 28 August 2001
# 2002 The Biochemical Society and the Medical Research Society
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